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Chemical Structure| 77-94-1 Chemical Structure| 77-94-1

Structure of Tributyl citrate
CAS No.: 77-94-1

Chemical Structure| 77-94-1

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Product Details of [ 77-94-1 ]

CAS No. :77-94-1
Formula : C18H32O7
M.W : 360.44
SMILES Code : O=C(CC(C(OCCCC)=O)(O)CC(OCCCC)=O)OCCCC
MDL No. :MFCD00027217
InChI Key :ZFOZVQLOBQUTQQ-UHFFFAOYSA-N
Pubchem ID :6507

Safety of [ 77-94-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 77-94-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 25
Num. arom. heavy atoms 0
Fraction Csp3 0.83
Num. rotatable bonds 17
Num. H-bond acceptors 7.0
Num. H-bond donors 1.0
Molar Refractivity 93.69
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

99.13 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

3.79
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

2.72
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.53
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

1.92
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

3.75
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.94

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.67
Solubility 0.777 mg/ml ; 0.00216 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-4.46
Solubility 0.0126 mg/ml ; 0.000035 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-3.99
Solubility 0.037 mg/ml ; 0.000103 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

No
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.57 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

1.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<2.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

3.57

Application In Synthesis of [ 77-94-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 77-94-1 ]
  • Downstream synthetic route of [ 77-94-1 ]

[ 77-94-1 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 77-92-9 ]
  • [ 71-36-3 ]
  • [ 77-94-1 ]
YieldReaction ConditionsOperation in experiment
95.3%
Stage #1: at 80℃; for 3 h; Inert atmosphere
Stage #2: at 130℃;
Step 1, Preparation of choline-based acidic ionic liquid: 0.5mol choline chloride was heated under agitation flask was added 500mL, 0.25mol of citric acid was added, under a nitrogen atmosphere, the conditions of temperature 80 3h, after cooling to give choline-based acidic ionic liquid;Step 2, the esterification reaction: to a stirred with a mechanical, a thermometer, a reflux condenser and a four-necked flask was added 1.0mol trap n-butanol and a step in the choline-based acidic ionic liquid was heated to reflux with stirring the reaction water was separated from the trap, the reaction of the reaction to dryness stopped when re-entering the trap, choline chloride precipitates from the reaction system; the stirring was heated at reflux temperature of 130 , the stirring rate to 1000rpm;Step 3, separated choline chloride: The reaction system of Step II reaction was filtered to obtain a solid product and a liquid phase of choline chloride;Step 4, tributyl citrate purification: step 3 of the liquid product was subjected to atmospheric distillation, and then using mass concentration of 8percent NaHCO3Mass concentration of the solution or NaOH solution (also can be mass concentration of 1percent to 3percent of 1percent to 5percent Na2CO3Alternatively the solution pH) after the residue was washed atmospheric distillation residue to a value of 6, followed by activated carbon was added to the residue decolorized after washing, the activated carbon was removed by filtration, and then the residue was distilled under reduced pressure after filtration, the pressure is 260 Pa, the fraction collected 197 ~ 200 obtain tributyl citrate; the atmospheric distillation temperature of 119 deg.] C; mass of the activated carbon was 5.0percent by mass of citric acid in step a.
94.1% at 95 - 143℃; for 6.33333 h; A 1 L four-necked flask equipped with a stirrer, thermometer, condenser and distillate receiver was charged with 192.0 g (1.0 mole) of anhydrous citric acid, 267.0 g (3.6 moles) of butanol and 1.9 g of sulfuric acid. The mixture was heated to 95°C over a period of 20 minutes while being stirred at atmospheric pressure. While recovering butanol and water generated as by-products of esterification in the receiver, stirring was continued for 3 hours until the reaction temperature reached 105°C. Subsequently, while recovering butanol and water generated as by-products of esterification in the receiver, 222.0 g (3.0 moles) of additional butanol was added at a reaction temperature of 101 to 143°C over a period of 3 hours to complete the reaction. After the completion of the reaction, the reaction product was cooled to 60°C, and at the same temperature (60°C), neutralized by adding sodium carbonate in an amount corresponding to twice the acid value of the reaction product (i.e., 2.0 g) and 120.0 g of water. Subsequently, the organic layer was washed with 120.0 g of water and heated to 120°C. Excess butanol was recovered until the pressure reached about 4 kPa, and steam distillation was performed at the same pressure at 120°C for 1 hour to remove low-boiling components from the reaction product, to thereby obtain 329.0 g of a colorless transparent liquid. The yield was 94.1percent and the acid value of the product was 0.025 (mg KOH/g).
84.4% With toluene-4-sulfonic acid In toluene at 90 - 110℃; for 4 h; With a stirrer,Trap,Snake-shaped condenser,Necked flask equipped with a stirrer and a thermometer, 3.6 mol (266.4 g) of n-butanol was added,Citric acid 0.6 mol (210 g),P-toluenesulfonic acid (9.53 g)Toluene 50 ml.During heating from 90 ° C to 110 ° C,From the first drop of water began to reflux for 4 hours.During the reaction, the lower water layer of the water separator was continuously released and measured with a graduated cylinderWater quantity.After the esterification reaction, the excess toluene and ethanol were distilled off under reduced pressure,The reaction product is then distilled under reduced pressure to give tributyl citrate.After completion of the reaction,The product esterification rate was 96.3percentThe yield of tributyl citrate was 84.4percent.
References: [1] Tetrahedron, 2006, vol. 62, # 2-3, p. 422 - 433.
[2] RSC Advances, 2018, vol. 8, # 66, p. 37835 - 37840.
[3] Angewandte Chemie - International Edition, 2009, vol. 48, # 1, p. 168 - 171.
[4] Green Chemistry, 2014, vol. 16, # 11, p. 4649 - 4653.
[5] Patent: CN104447306, 2016, B, . Location in patent: Paragraph 0044-0048; 0052.
[6] Patent: EP1491523, 2004, A1, . Location in patent: Page 16.
[7] RSC Advances, 2014, vol. 4, # 100, p. 57297 - 57307.
[8] Patent: CN106278881, 2017, A, . Location in patent: Paragraph 0017; 0018.
[9] Archives of Biochemistry, 1950, vol. 28, p. 274,275.
[10] Industrial and Engineering Chemistry, 1955, vol. 47, p. 797.
[11] Journal of Pharmacy and Pharmacology, 1950, vol. 2, p. 229.
[12] Bulletin of the Chemical Society of Ethiopia, 2011, vol. 25, # 1, p. 147 - 150.
  • 2
  • [ 109-69-3 ]
  • [ 68-04-2 ]
  • [ 77-94-1 ]
References: [1] Patent: CN105237396, 2016, A, . Location in patent: Paragraph 0017.
  • 3
  • [ 77-92-9 ]
  • [ 71-36-3 ]
  • [ 118068-28-3 ]
  • [ 142-96-1 ]
  • [ 77-94-1 ]
  • [ 101996-65-0 ]
References: [1] Patent: EP1849764, 2007, A1, . Location in patent: Page/Page column 21-22.
  • 4
  • [ 298-12-4 ]
  • [ 71-36-3 ]
  • [ 105-76-0 ]
  • [ 2050-60-4 ]
  • [ 141-03-7 ]
  • [ 1587-18-4 ]
  • [ 344268-32-2 ]
  • [ 38094-11-0 ]
  • [ 77-94-1 ]
  • [ 105-75-9 ]
  • [ 117538-83-7 ]
  • [ 94086-70-1 ]
References: [1] Chemistry and Biodiversity, 2012, vol. 9, # 4, p. 714 - 726.
  • 5
  • [ 7664-93-9 ]
  • [ 77-92-9 ]
  • [ 71-36-3 ]
  • [ 77-94-1 ]
References: [1] Industrial and Engineering Chemistry, 1955, vol. 47, p. 797.
 

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